Seladelpar approved in Canada as Lyvdelzi to treat adults with PBC
Therapy can be used in combo, or by patients who can't tolerate UDCA
Health Canada has conditionally approved Gilead Sciences’ seladelpar — to be marketed in the country under the brand name Lyvdelzi — as a second-line therapy for adults with primary biliary cholangitis (PBC).
The oral treatment is cleared for use in combination with the first-line PBC therapy ursodeoxycholic acid (UDCA) in patients who don’t adequately respond to UDCA alone, or as a single therapy in those who can’t tolerate UDCA.
With this approval, the therapy will soon become available to the estimated 13,000 Canadians who live with the rare liver disease — most of whom are women older than 40.
“The approval of Lyvdelzi marks an important milestone, offering a new choice with a distinct profile that may help address unmet needs,” Paul Petrelli, general manager at Gilead Sciences Canada, said in a company press release. “We’re proud to build on Gilead’s deep heritage in liver disease and are committed to ensuring Canadian patients who could benefit from Lyvdelzi have access to it.”
With conditional, or accelerated, approvals, regulators permit the marketing of an experimental therapy based on preliminary clinical evidence, with full approval contingent upon additional trial data confirming its benefits.
Seladelpar, under the brand name Livdelzi, had previously received conditional approval in the U.S. and full approval in the U.K. for the same indication. Additionally, the therapy was conditionally approved in the European Union, also as Lyvdelzi, for the same patient population.
PBC is a type of cholangitis, a condition marked by inflammation of the bile ducts — the tubes that carry the digestive fluid bile from the liver into the small intestine. Over time, inflammatory damage to the ducts disrupts bile flow, causing it to build to toxic levels in the liver and leak into the bloodstream, leading to itchy skin, known as pruritus, fatigue, and other symptoms.
Lyvdelzi approval mainly based on Phase 3 RESPONSE trial data
Gail Wright, who was diagnosed with PBC in 2012 and is the president of the Canadian PBC Society, noted that “those living with PBC share common symptoms, including incessant itching or skin-crawling sensations, as well as debilitating fatigue that is made worse at night.”
The Health Canada decision “represents meaningful progress in expanding treatment options and improving our quality of life,” Wright said. “I welcome the approval of this new treatment.”
UDCA, marketed as Actigall and Urso in the U.S. and available as generics, remains the first-line PBC therapy. However, as many as 40% of patients don’t adequately respond or are intolerant to it, according to Gilead.
Available as oral capsules, Lyvdelzi is designed to activate PPAR-delta, a protein that helps regulate the production of bile acids, the main component of bile. By activating PPAR-delta, Lyvdelzi reduces bile acid production in the liver, which is expected to lessen inflammation and ease PBC symptoms.
Current therapies have limitations optimally addressing both disease progression and symptom burden. … In a rigorous Phase 3 trial setting, Lyvdelzi was the first PBC medicine to meet both of these critical needs with statistical significance.
Lyvdelzi’s conditional approval in Canada mainly draw on data from the Phase 3 RESPONSE clinical trial (NCT04620733). The now-completed study tested the therapy, taken once daily, against a placebo for one year in 193 adults with PBC who didn’t fully respond to or couldn’t tolerate UDCA.
At one year, more than three times as many PBC patients treated with Lyvdelzi achieved a biochemical response — defined as a reduction in blood levels of two liver damage biomarkers — than those given a placebo (62% vs. 20%).
Secondary measures showed that alkaline phosphatase, a marker for liver damage, reached normal levels in one-quarter of Lyvdelzi-treated patients versus none in the placebo group. In addition, those with moderate to severe itching at the study’s start experienced a significant and clinically meaningful reduction in this symptom compared with those on the placebo.
“Current therapies have limitations optimally addressing both disease progression and symptom burden,” said Gideon Hirschfield, PhD, director of the autoimmune and rare liver disease program at Toronto General Hospital in Canada and a lead investigator of RESPONSE. “In a rigorous Phase 3 trial setting, Lyvdelzi was the first PBC medicine to meet both of these critical needs with statistical significance.”
Advocate says approval will help ‘personalize treatment’ in PBC
The most common adverse events with the therapy, reported in at least 5% of Lyvdelzi-treated patients and at higher rates than in the placebo group, were headache, nausea, dizziness, and abdominal pain and swelling.
As a patient, Wright said Lyvdelzi’s approval may allow better treatment for those living with PBC.
“The availability of a new treatment option that addresses both biochemical markers and helps reduce intense itching is a milestone for our community allowing clinicians to better personalize treatment for people with PBC,” Wright said.
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